Ultrasound activatable antiangiogenic sonosensitizer for VEGFR associated glioblastoma tumor models

Subin Son; Chuangli Zhang; Miae Won; Paramesh Jangili; Minhyeok Choi; Jiasheng Wu; Jong Seung Kim

doi:10.1002/agt2.97

Ultrasound activatable antiangiogenic sonosensitizer for VEGFR associated glioblastoma tumor models

Subin Son, Chuangli Zhang, Miae Won, Paramesh Jangili, Minhyeok Choi, Jiasheng Wu, Jong Seung Kim

Research output: Contribution to journal › Article › peer-review

9 Citations (Scopus)

Abstract

Angiogenic signaling pathway is a major contributing factor in cancer recurrence and progression, which can cause significantly reduced treatment outcomes, especially in the oxygen-dependent photo- and sonodynamic therapies. VEGF and its receptor (VEGFR) play a crucial role in angiogenesis progression; precisely, upregulated VEGF signaling is mainly associated with angiogenesis progression in many types of cancers. Herein, we report a sunitinib-conjugated sonosensitizer (TK-RB: tyrosine kinase-rose bengal) to enhance the anticancer efficacy through VEGF inhibition-mediated antiangiogenesis in conjunction with cellular/tumor damage by ROS generated under ultrasound irradiation. TK-RB reveals good selectivity and cytotoxicity toward VEGFR-positive cells (U87MG) over VEGFR-negative cells (MCF-7). The fluorescent imaging analysis in vivo/ex vivo and the tumor growth investigation in nude mice with U87MG glioblastoma tumor xenografts demonstrate that rose bengal having tyrosine kinase inhibitor (TK-RB) provides an enhanced antitumor effect. The current strategy will make a great contribution to optimizing anticancer performance by utilizing sonodynamic therapy together with antiangiogenics in several different malignancies.

Original language	English
Article number	e97
Journal	Aggregate
Volume	2
Issue number	4
DOIs	https://doi.org/10.1002/agt2.97
Publication status	Published - 2021 Aug

Bibliographical note

Funding Information:
This work was supported by the National Research Foundation of Korea (CRI Project No. 2018R1A3B1052702 and 2019M3E5D1A01068998, Jong Seung Kim), Basic Science Research Program (2020R1A6A3A01100551, Miae Won) funded by the Ministry of Education, and National Natural Science Foundation of China (Grant no. 21673265, Jiasheng Wu).

Publisher Copyright:
© 2021 The Authors. Aggregate published by John Wiley & Sons Australia, Ltd on behalf of South China University of Technology and AIE Institute.

Keywords

antiangiogenesis
glioblastoma
sonodynamic therapy
VEGFR blockage

ASJC Scopus subject areas

Chemistry (miscellaneous)
Materials Science (miscellaneous)
Materials Chemistry
Molecular Biology

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1002/agt2.97

Cite this

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title = "Ultrasound activatable antiangiogenic sonosensitizer for VEGFR associated glioblastoma tumor models",

abstract = "Angiogenic signaling pathway is a major contributing factor in cancer recurrence and progression, which can cause significantly reduced treatment outcomes, especially in the oxygen-dependent photo- and sonodynamic therapies. VEGF and its receptor (VEGFR) play a crucial role in angiogenesis progression; precisely, upregulated VEGF signaling is mainly associated with angiogenesis progression in many types of cancers. Herein, we report a sunitinib-conjugated sonosensitizer (TK-RB: tyrosine kinase-rose bengal) to enhance the anticancer efficacy through VEGF inhibition-mediated antiangiogenesis in conjunction with cellular/tumor damage by ROS generated under ultrasound irradiation. TK-RB reveals good selectivity and cytotoxicity toward VEGFR-positive cells (U87MG) over VEGFR-negative cells (MCF-7). The fluorescent imaging analysis in vivo/ex vivo and the tumor growth investigation in nude mice with U87MG glioblastoma tumor xenografts demonstrate that rose bengal having tyrosine kinase inhibitor (TK-RB) provides an enhanced antitumor effect. The current strategy will make a great contribution to optimizing anticancer performance by utilizing sonodynamic therapy together with antiangiogenics in several different malignancies.",

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author = "Subin Son and Chuangli Zhang and Miae Won and Paramesh Jangili and Minhyeok Choi and Jiasheng Wu and Kim, {Jong Seung}",

note = "Funding Information: This work was supported by the National Research Foundation of Korea (CRI Project No. 2018R1A3B1052702 and 2019M3E5D1A01068998, Jong Seung Kim), Basic Science Research Program (2020R1A6A3A01100551, Miae Won) funded by the Ministry of Education, and National Natural Science Foundation of China (Grant no. 21673265, Jiasheng Wu). Publisher Copyright: {\textcopyright} 2021 The Authors. Aggregate published by John Wiley & Sons Australia, Ltd on behalf of South China University of Technology and AIE Institute.",

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AU - Choi, Minhyeok

AU - Wu, Jiasheng

AU - Kim, Jong Seung

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PY - 2021/8

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N2 - Angiogenic signaling pathway is a major contributing factor in cancer recurrence and progression, which can cause significantly reduced treatment outcomes, especially in the oxygen-dependent photo- and sonodynamic therapies. VEGF and its receptor (VEGFR) play a crucial role in angiogenesis progression; precisely, upregulated VEGF signaling is mainly associated with angiogenesis progression in many types of cancers. Herein, we report a sunitinib-conjugated sonosensitizer (TK-RB: tyrosine kinase-rose bengal) to enhance the anticancer efficacy through VEGF inhibition-mediated antiangiogenesis in conjunction with cellular/tumor damage by ROS generated under ultrasound irradiation. TK-RB reveals good selectivity and cytotoxicity toward VEGFR-positive cells (U87MG) over VEGFR-negative cells (MCF-7). The fluorescent imaging analysis in vivo/ex vivo and the tumor growth investigation in nude mice with U87MG glioblastoma tumor xenografts demonstrate that rose bengal having tyrosine kinase inhibitor (TK-RB) provides an enhanced antitumor effect. The current strategy will make a great contribution to optimizing anticancer performance by utilizing sonodynamic therapy together with antiangiogenics in several different malignancies.

AB - Angiogenic signaling pathway is a major contributing factor in cancer recurrence and progression, which can cause significantly reduced treatment outcomes, especially in the oxygen-dependent photo- and sonodynamic therapies. VEGF and its receptor (VEGFR) play a crucial role in angiogenesis progression; precisely, upregulated VEGF signaling is mainly associated with angiogenesis progression in many types of cancers. Herein, we report a sunitinib-conjugated sonosensitizer (TK-RB: tyrosine kinase-rose bengal) to enhance the anticancer efficacy through VEGF inhibition-mediated antiangiogenesis in conjunction with cellular/tumor damage by ROS generated under ultrasound irradiation. TK-RB reveals good selectivity and cytotoxicity toward VEGFR-positive cells (U87MG) over VEGFR-negative cells (MCF-7). The fluorescent imaging analysis in vivo/ex vivo and the tumor growth investigation in nude mice with U87MG glioblastoma tumor xenografts demonstrate that rose bengal having tyrosine kinase inhibitor (TK-RB) provides an enhanced antitumor effect. The current strategy will make a great contribution to optimizing anticancer performance by utilizing sonodynamic therapy together with antiangiogenics in several different malignancies.

KW - antiangiogenesis

KW - glioblastoma

KW - sonodynamic therapy

KW - VEGFR blockage

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Ultrasound activatable antiangiogenic sonosensitizer for VEGFR associated glioblastoma tumor models

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

UN SDGs

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